DESCRIPTION (Verbatim from the Applicant's Abstract): This Phase I SBIR application seeks support to develop and evaluate a naturally-occurring extracellular matrix (ECM) bioscaffold material for tissue engineering applications; specifically, the repair and/or restoration of congenital defects in which lost or missing tissue is the limiting factor for surgical reconstruction. Porcine derived ECM harvested from the urinary bladder (UBM) represents a cellular biodegradable scaffold material that supports cell attachment, migration, proliferation and differentiation, and wound healing. Processed single sheets of UBM and other ECMs have shown excellent remodeling capabilities in both pre clinical animal studies and early human clinical studies. With SBIR Phase I support, we propose to develop a multilaminate sheet form of UBM with the appropriate mechanical and biologic properties that allow for post surgical tissue growth and thus obviate the need for repeat surgeries as the patient matures. An experimentally-created diaphragmatic hernia will be used as the model of a congenital defect. There are three specific aims. First, we will determine the manufacturing method required to develop a prototype multilaminate UBM device with the mechanical strength that exceeds by a factor of 2 the normal mammalian diaphragm. Secondly, we will evaluate the effect of two different methods of sterilization, gamma irradiation and ethylene oxide, upon the mechanical strength of the prototype UBM device. The third specific aim will evaluate the utility of the sterilized multilaminate UBM device in a dog pilot study in which an experimentally-created diaphragmatic hernia will be repaired in 10-weekold dogs and evaluated over time until the point of physical maturity. Currently, there are limited options for the surgical repair/reconstruction of body structures that require surgical repair as a result of congenital abnormalities. The proposed studies are critical in the decision-making process of determining whether or not to pursue development of this product. Each objective/specific aim has well-defined criteria for success, and the proposed studies will be conducted by an experienced and knowledgeable tissue engineering research team. A time line for the proposed work is provided, and the technology involves an innovative tissue engineering approach in a medical field with significant unmet needs. PROPOSED COMMERCIAL APPLICATION: The use of UBM-ECM for the tissue engineering applications that involve the restoration of missing tissue as a result of congenital anomalies is in many ways an orphan market. Most biomaterials currently available for such use are inadequate beause they do not "grow" as the infant grows and, thus, repeat surgical procedures are required. Many currently available materials result in scar tissue formation with extensive morbidity. The development of new materials for these applications is not cost effective for many large companies due to the relatively small number of patients requiring this material each year. However, these patients desperately need a better alternative to existing materials, and successful development of this product could lead to broader surgical applications.